Imbalance Between Soluble and Membrane-Bound CD100 Regulates Monocytes Activity in Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure

CD100 is an important immune semaphorin that is a secreted and membrane bound protein involved in infectious diseases. However, CD100 expression profile and the regulation to innate immune system in hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) was not previously reported. The aim of this study was to investigate CD100 level and modulatory function of CD100 to CD14(+) monocytes in HBV-ACLF patients. Plasma-soluble CD100 (sCD100) level and membrane-bound CD100 (mCD100) expression on peripheral CD14(+) monocytes was analyzed in HBV-ACLF patients. CD14(+) monocytes-induced cytotoxicity and CD14(+) monocytes-mediated T cell activation in response to CD100 stimulation was also assessed in direct and indirect contact coculture culture systems. HBV-ACLF patients had lower plasma sCD100 and higher mCD100 level on CD14(+) monocytes compared with asymptomatic HBV carriers, chronic hepatitis B patients, and controls. CD14(+) monocytes from HBV-ACLF patients induced limited target Huh7.5 cell death and secreted less interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granzyme B in both direct and indirect contact coculture systems compared with controls. Recombinant sCD100 not only enhanced CD14(+) monocytes-mediated Huh7.5 cell death and granzyme B secretion, but it also elevated CD14(+) monocytes-induced IFN-gamma/interleukin-17 production by CD4(+) T cells as well as IFN-gamma/TNF-alpha secretion by CD8(+) T cells in HBV-ACLF patients. The current data indicated that severe inflammation induced sCD100/mCD100 imbalance to inactivate CD14(+) monocytes response, which might be beneficial for the survival of HBV-ACLF patients.